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in vivo

NOT Open Access | Artemisinin Cocrystals for Bioavailability Enhancement. Part 2: In Vivo Bioavailability and Physiologically Based Pharmacokinetic Modeling

December 7, 2021 - 21:16 -- NOT Open Access
Kaur M, Yardley V, Wang K, Masania J, Arroo RRJ, Turner DB, Li M
Mol Pharm. 2021 Dec 6;18(12):4272-4289

We report the evaluation and prediction of the pharmacokinetic (PK) performance of artemisinin (ART) cocrystal formulations, that is, 1:1 artemisinin/orcinol (ART-ORC) and 2:1 artemisinin/resorcinol (ART2-RES), using in vivo murine animal and physiologically based pharmacokinetic (PBPK) models. The efficacy of the ART cocrystal formulations along with the parent drug ART was tested in mice infected with Plasmodium berghei.

Design of proteasome inhibitors with oral efficacy in vivo against Plasmodium falciparum and selectivity over the human proteasome

October 5, 2021 - 10:41 -- Open Access
Xie SC, Metcalfe RD, Tilley L, et al.
Proc Natl Acad Sci U S A. 2021 Sep 28;118(39):e2107213118

The Plasmodium falciparum proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates that are potent and specific inhibitors of the P. falciparum 20S proteasome (Pf20S) β5 active site and that exhibit fast-acting antimalarial activity. They selectively inhibit the growth of P. falciparum compared with a human cell line and exhibit high potency against field isolates of P. falciparum and Plasmodium vivax They have a low propensity for development of resistance and possess liver stage and transmission-blocking activity.

NOT Open Access | Novel Antiplasmodial Compounds Leveraged with Multistage Potency against the Parasite Plasmodium falciparum: In Vitro and In Vivo Evaluations and Pharmacokinetic Studies

June 16, 2021 - 09:52 -- NOT Open Access
Sharma N, Kashif M, Singh V, Fontinha D, Mukherjee B, Kumar D, Singh S, Prudencio M, Singh AP, Rathi B
J Med Chem. 2021 Jun 14

Hydroxyethylamine (HEA)-based novel compounds were synthesized and their activity against Plasmodium falciparum 3D7 was assessed, identifying a few hits without any apparent toxicity. Hits 5c and 5d also exhibited activity against resistant field strains, PfRKL-9 and PfC580Y. A single dose, 50 mg/Kg, of hits administered to the rodent parasite Plasmodium berghei ANKA exhibited up to 70% reduction in the parasite load.

Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum

February 25, 2021 - 10:12 -- Open Access
Pholcharee T, Oyen D, Wilson IA, et al.
Nat Commun. 2021 Feb 16;12(1):1063

The most advanced P. falciparum circumsporozoite protein-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable antibody responses. Here, we elucidate crystal structures, binding affinities and kinetics, and in vivo protection of eight anti-NANP antibodies derived from an RTS,S phase 2a trial and encoded by three different heavy-chain germline genes.

Diatretol, an α, α'-dioxo-diketopiperazine, is a potent in vitro and in vivo antimalarial

January 19, 2021 - 16:04 -- Open Access
Ishiyama A, Hokari R, Nonaka K, Chiba T, Miura H, Otoguro K, Iwatsuki M
J Antibiot (Tokyo). 2021 Jan 14:1-3

A fungal metabolite, diatretol, has shown to be a promising antimalarial agent.

Anti-Oxidant Potential and Antimalarial Effects of Acanthus polystachyus Delile (Acanthaceae) Against Plasmodium berghei: Evidence for in vivo Antimalarial Activity

December 23, 2020 - 10:32 -- Open Access
Kifle ZD, Atnafie SA
J Exp Pharmacol. 2020 Dec 11;12:575-587

Malaria is among the most devastating and widespread tropical parasitic diseases which is more prevalent in developing countries. Acanthus polystachyus (Acanthaceae) leaves are traditionally used for the treatment of malaria in Ethiopia. This study aimed to investigate the in vivo antimalarial and in vitro antioxidant activity of the leaves extract of Acanthus polystachyus.

NOT Open Access | Plasmodium falciparum purine nucleoside phosphorylase as a model in the search for new inhibitors by high throughput screening

December 16, 2020 - 10:06 -- NOT Open Access
Holanda RJ, Deves C, Pereira da Silva LH, et al.
Int J Biol Macromol. 2020 Dec 15;165(Pt B):1832-1841

Studies have shown that inhibition of Plasmodium falciparum Purine Nucleoside Phosphorylase (PfPNP) blocks the purine salvage pathway in vitro and in vivo. In this study, PfPNP was evaluated as a model in the search for new inhibitors using surface plasmon resonance (SPR). Its expression, purification, oligomeric state, kinetic constants, calorimetric parameters and kinetic mechanisms were obtained. PfPNP was immobilized on a CM5 sensor chip and sensorgrams were produced through binding the enzyme to the substrate MESG and interactions between molecules contained in 10 fractions of natural extracts.

NOT Open Access | Assessment of in vitro and in vivo antimalarial efficacy and GC-fingerprints of selected medicinal plant extracts

December 2, 2020 - 08:38 -- NOT Open Access
Sachdeva C, Mohanakrishnan D, Kumar S, Kaushik NK
Exp Parasitol. 2020 Dec;219:108011

A hallmark of mortality and morbidity, malaria is affecting nearly half of the world's population. Emergence of drug-resistant strains of malarial parasite prompts identification and evaluation of medicinal plants and their constituents that may hold the key to a new and effective anti-malarial drug. In this context, nineteen methanolic extracts from seventeen medicinal plants were evaluated for anti-plasmodial potential against Plasmodium falciparum strain 3D7 (Chloroquine (CQ) sensitive) and INDO (CQ resistant) using fluorescence based SYBR-Green assay and for cytotoxic effects against mammalian cell lines.

Evaluation of in vivo anti-malarial potential of omidun obtained from fermented maize in Ibadan, Nigeria

November 24, 2020 - 13:42 -- Open Access
Favour O. Omeiza, George O. Ademowo and Funmilola A. Ayeni
Malaria Journal 2020 19:414, 19 November 2020

The menace of resistance to anti-malarial drugs is a great challenge to malaria control, necessitating the search for new anti-malarial agents. This search has led to the exploration of natural products for efficacy in malaria therapy. Omidun is the supernatant of fermenting maize (ogi) slurry that has been widely investigated and reported to possess several health benefits and it is used traditionally as solvent for preparing anti-malarial herbs. However, there is no information on the anti-malarial activity of omidun itself. This study was conducted to investigate the prophylactic, curative and suppressive anti-malarial potential of omidun.

Plasmodium berghei K13 Mutations Mediate In Vivo Artemisinin Resistance That Is Reversed by Proteasome Inhibition

November 11, 2020 - 14:33 -- Open Access
Simwela NV, Stokes BH, Aghabi D, Bogyo M, Fidock DA, Waters AP
mBio. 2020 Nov 10;11(6):e02312-20

The recent emergence of Plasmodium falciparum parasite resistance to the first line antimalarial drug artemisinin is of particular concern. Artemisinin resistance is primarily driven by mutations in the P. falciparum K13 protein, which enhance survival of early ring-stage parasites treated with the artemisinin active metabolite dihydroartemisinin in vitro and associate with delayed parasite clearance in vivo However, association of K13 mutations with in vivo artemisinin resistance has been problematic due to the absence of a tractable model.


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